A heteroporous model of the glomerular filtration barrier was developed and used to interpret dextransieving data in healthy volunteers (normal controls), in patients with nephrotic range proteinuria (grouped as grades I-III, according to severity), and in a group of previously nephrotic patients whose proteinuria was in remission ("resolved controls"). Several hypothetical pore-size distributions were compared in terms of their ability to describe the selective increases in the fractional clearance of large dextrans observed with increasing severity of proteinuria. The most successful model examined was based on the assumption that the major portion of the capillary wall functions as an isoporous membrane, but that a small fraction of the filtrate passes through pores that are unable to discriminate among dextrans of different sizes. The value of the membrane parameter that reflects the relative importance of the nonselective pores was found to increase in parallel with the fractional clearance of immunoglobulin G; it increased progressively in going from normal controls to resolved controls to grades I-III nephrotics. The observed patterns of protein excretion could not, however, be explained entirely by a loss of glomerular size selectivity. Variations in membrane selectivity on the basis of molecular charge and/or molecular configuration are also likely to have been important.

In 26 Wistar rats with surface glomeruli, the determinants of glomerular ultrafiltration and peritubular capillary uptake of proximal reabsorbate were studied before and during intravenous infusions of norepinephrine or angiotensin II. Regardless of whether renal perfusion pressure (AP) was permitted to increase, both hormones produced elevations in single nephron filtration fraction due to declines in glomerular plasma flow with little change in nephron glomerular filtration rate. The resulting large increases in the efferent arteriolar oncotic pressure, ir E , were accompanied by equivalent increases in the mean glomerular transcapillary hydraulic pressure difference, AP. Equality of TT E and AP, denoting filtration pressure equilibrium, obtained before and during infusion of either hormone. For both hormones, when elevations in AP were allowed, marked and roughly proportional increases in the resistance to blood flow through single afferent and efferent arterioles occurred, whereas when increases in AP were prevented by partial aortic constriction increases in resistance were confined primarily to the efferent arteriole. Despite the marked increases in -w E , absolute rates of proximal tubule fluid reabsorption, on the average, were unchanged by these hormones due to the opposing effects of marked decreases in efferent arteriolar plasma flow rate and, to a lesser extent, increases in peritubular capillary hydraulic pressure.• It has long been appreciated that the hydraulic pressure of the blood flowing through the mammalian kidney declines from a maximum value of approximately 120 mm Hg in the renal artery to roughly 10 mm Hg by the time the blood enters the peritubular capillary bed. Some two-thirds of this axial pressure drop occurs prior to the division of the afferent arterioles into the tufts of capillaries that compose single glomeruli (1-9). Since the afferent arteriolar blood flow rate is not very much greater than that in the efferent arterioles, the greater axial pressure drop along the afferent arteriole clearly indicates a resistance to blood flow along this vessel larger than that along the efferent arteriole.Prior to the availability of methods and animal species permitting direct measurements of these hydraulic pressure profiles, numerous investigators Received January 9, 1975. Accepted for publication April 23, 1975 Circulation Research, Vol. 37, July 1975 (10-21) used a variety of vasoactive substances in an effort to identify the relative contributions of these pre-and postglomerular vascular resistances to the overall regulation of renal blood flow and glomerular filtration rate. The generally accepted interpretation of results of such studies is that the filtration fraction and the glomerular filtration rate are primarily dependent on the mean transcapillary hydraulic pressure difference, AP, which is thought to be altered by changes in either afferent or efferent arteriolar tone. For example, if a vasoactive substance causes constriction of the afferent arteriole, thereby incre...

In 23 Munich-Wistar rats with surface glomeruli, the determinants of glomerular ultrafiltration and peritubular capillary uptake of proximal reabsorbate were studied before and during intra-arterial infusions of mildly vasodepressor doses of prostaglandin E1,acetylcholine, and bradykinin. For each drug single-nephron glomerular filtration rate remained unchanged from normal hydropenic values while glomerular plasma flow rate increased, resulting in declines in single-nephron filtration fraction (SNFF). Mean glomerular transcapillary hydraulic pressure difference (delta P) increased or remained unchanged on average. Declines in SNFF were accompanied by reductions in efferent arteriolar oncotic pressure (piE). Filtration pressure equilibrium, equality between pi E and delta P, obtained before but not during drug infusions. In the latter situation values for the glomerular capillary ultrafiltration coefficient were calculated and found to be significantly reduced from published control values. Despite marked falls in pi E during drug infusion, absolute proximal reabsorption was not reduced significantly, due, it is suggested, to the opposing effects of increases in efferent arteriolar plasma flow and interstitial hydraulic pressure.

Ten postcardiac surgical patients with acute renal failure (ARF) were infused with inulin and dextran 40. Plasma and urine were then submitted to gel-permeation chromatography to ascertain the apparent fractional clearance profile for the dextrans. Compared to normal volunteer controls, the fractional clearance profile was substantially elevated for dextran molecules in the Einstein-Stokes radius (r) range 20-40 A. For the smaller molecules (r = 20-28 A), fractional dextran clearance in ARF was frequently in excess of unity. A simple mass conservation model which assumes that the "true" fractional dextran clearance profile for the glomerulus (in Bowman's space) in ARF is the same as that for normal controls, when applied to the experimental observations, revealed that in ARF, on the average, 50% of filtered inulin is lost by tubular backleakage. Furthermore, the model permitted an estimate of the permeability properties of the damaged tubular wall. This indicated tubular permeability not unlike that of the normal glomerulus to dextran molecules with r less than 30 A, but relative impermeability to larger dextran molecules.

Hladunewich MA, Myers BD, Derby GC, Blouch KL, Druzin ML, Deen WM, Naimark DM, Lafayette RA. Course of preeclamptic glomerular injury after delivery. Am J Physiol Renal Physiol 294: F614-F620, 2008. First published January 16, 2008 doi:10.1152/ajprenal.00470.2007.-We evaluated the early postpartum recovery of glomerular function over 4 wk in 57 women with preeclampsia. We used physiological techniques to measure glomerular filtration rate (GFR), renal plasma flow, and oncotic pressure ( A) and computed a value for the two-kidney ultrafiltration coefficient (Kf). Compared with healthy, postpartum controls, GFR was depressed by 40% on postpartum day 1, but by only 19% and 8% in the second and fourth postpartum weeks, respectively. Hypofiltration was attributable solely to depression, at corresponding postpartum times, of Kf by 55%, 30%, and 18%, respectively. Improvement in glomerular filtration capacity was accompanied by recovery of hypertension to near-normal levels and significant improvement in albuminuria. We conclude that the functional manifestations of the glomerular endothelial injury of preeclampsia largely resolve within the first postpartum month. glomerular filtration rate; ultrafiltration coefficient; postpartum recovery AFFECTING 5-7% of pregnancies, preeclampsia remains a leading cause of maternal and fetal morbidity and mortality. Because the primary target of injury in preeclampsia is the glomerular endothelial cell, affected patients invariably present with depression of the glomerular filtration rate (GFR), proteinuria, and hypertension. We previously (13) evaluated glomerular morphology immediately after delivery. We demonstrated severe endothelial cell swelling with diminished size and density of the endothelial fenestrae, along with mesangial cell interposition and subendothelial fibrinoid deposits. These findings were computed to lower glomerular filtration capacity sufficiently to account for the observed depression of GFR by 40% (13).Despite the profound alterations in glomerular morphology, clinical recovery is usually rapid after delivery of the placenta. However, few detailed physiological evaluations of preeclampsia have been undertaken in the postpartum period. The characteristic glomerular pathological lesion has been reported to improve within days after delivery (21). Although complete recovery can occasionally require in excess of 6 mo, the majority of cases demonstrate complete resolution of the renal pathology within 3 mo (25). With the exception of those women with persistent postpartum hypertension, GFR and proteinuria also normalize over several months (18,(32)(33)(34).In the present study, we have employed precise physiological techniques to evaluate the postpartum course of the GFR and its determinants in women with preeclampsia. We combined our physiological findings with mathematical modeling to estimate glomerular ultrafiltration capacity. We observed a profound initial injury, which improved significantly after 4 wk. METHODSPatient population. This paper represents a...